Metabolomics analysis revealed significantly higher synovial Phe/Tyr ratio in reactive arthritis and undifferentiated spondyloarthropathy

Muhammed, Hafis; Kumar, Dinesh; Dubey, Durgesh; Kumar, Sandeep; Chaurasia, Smriti; Guleria, Anupam; Majumder, Sanjukta; Singh, Rajeev; Agarwal, Vikas; Misra, Ramnath

doi:10.1093/rheumatology/kez493

Cited by 14 publications

(18 citation statements)

References 7 publications

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“…The pathophysiological states, that is, oxidative stress and inflammation, were further indicated by the elevated serum levels of PTR and NAG as per previous reports. 35,51 The summary of these metabolic pathway alterations is shown in Figure 5.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…These metabolites are 3-hydroxybutyrate, lactate, acetate, citrate, acetoacetate, pyruvate, succinate, alanine, betaine, creatine, creatinine, glutamine, glutamate, glucose, glycine, leucine, isoleucine, valine, proline, phenylalanine, threonine, tyrosine, histidine, trimethylamine- N -oxide (TMAO), and myo-inositol. As described previously, − these concentrations were further used to estimate other four relevant metabolic ratios such as glutamate to glutamine ratio (EQR), phenylalanine to tyrosine ratio (PTR), branched-chain amino acid to tyrosine ratio [BTR also referred as Fischer ratio; estimated as (leucine + isoleucine + valine)/tyrosine], , and lactate-to-pyruvate ratio (LPR). The estimated mean and median values of these 29 serum metabolic features are tabulated in the Supporting Information (Table S2).…”

Section: Resultsmentioning

confidence: 99%

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Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach

et al. 2022

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Detection of metabolic disturbances in lung cancer (LC) has the potential to aid early diagnosis/prognosis and hence improve disease management strategies through reliable grading, staging, and determination of neoadjuvant status in LC. However, a majority of previous metabolomics studies compare the normalized spectral features which not only provide ambiguous information but further limit the clinical translation of this information. Various such issues can be resolved by performing the concentration profiling of various metabolites with respect to formate as an internal reference using commercial software Chenomx. Continuing our efforts in this direction, the serum metabolic profiles were measured on 39 LC patients and 42 normal controls (NCs, comparable in age/sex) using high-field 800 MHz NMR spectroscopy and compared using multivariate statistical analysis tools to identify metabolic disturbances and metabolites of diagnostic potential. Partial least-squares discriminant analysis (PLS-DA) model revealed a distinct separation between LC and NC groups and resulted in excellent discriminatory ability with the area under the receiver-operating characteristic (AUROC) = 0.97 [95% CI = 0.89–1.00]. The metabolic features contributing to the differentiation of LC from NC samples were identified first using variable importance in projection (VIP) score analysis and then checked for their statistical significance (with p-value < 0.05) and diagnostic potential using the ROC curve analysis. The analysis revealed relevant metabolic disturbances associated with LC. Among various circulatory metabolites, six metabolites, including histidine, glutamine, glycine, threonine, alanine, and valine, were found to be of apposite diagnostic potential for clinical implications. These metabolic alterations indicated altered glucose metabolism, aberrant fatty acid synthesis, and augmented utilization of various amino acids including active glutaminolysis in LC.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach

et al. 2022

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“…5 studies included JIA patients (Zeft et al, 2014;Stoll et al, 2016;Butbul et al, 2020;Vernocchi et al, 2020;Funk and Becker, 2021). 5 studies included ReA patients (Ahmed et al, 2019;Guleria et al, 2019;Li et al, 2019;Muhammed et al, 2020;Dubey et al, 2021). 2 studies included uSpA patients (Ahmed et al, 2019;Muhammed et al, 2020), 1 study included ERA patients (Stoll et al, 2016), 1 study included IBD-SpA (Berlinberg et al, 2021).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…5 studies included ReA patients (Ahmed et al, 2019;Guleria et al, 2019;Li et al, 2019;Muhammed et al, 2020;Dubey et al, 2021). 2 studies included uSpA patients (Ahmed et al, 2019;Muhammed et al, 2020), 1 study included ERA patients (Stoll et al, 2016), 1 study included IBD-SpA (Berlinberg et al, 2021). 1 study enrolled cases with mixed subtypes of SpA without describing a specific subtype (Gupta et al, 2021).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…Nineteen studies assessed the metabolome by serum/plasma. Feces (Shao et al, 2016;Stoll et al, 2016;He et al, 2019;Vernocchi et al, 2020), urine (Kapoor et al, 2013;Nanus et al, 2015;Wang et al, 2016;Butbul et al, 2020), and synovial fluid (Ahmed et al, 2019;Li et al, 2019;Muhammed et al, 2020;Dubey et al, 2021) were commonly studied in these metabolomic researches. In addition, tissues such as ligament tissue (Wang et al, 2016), colon biopsies (Berlinberg et al, 2021), synovial membrane tissue (Rocha et al, 2021), saliva (Lv et al, 2021), and exhaled breath (Zeft et al, 2014) were also used for analysis in 1 study each.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

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Metabolomic analysis in spondyloarthritis: A systematic review

Huang

Pu²,

Wang³

et al. 2022

Front. Microbiol.

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Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent years. We conducted a systematic review to provide a collective summary of previous findings on metabolomic profiling associated with SpA. We systematically searched PubMed, Medline, Embase and Web of Science for studies on comparisons of the metabolomic analysis of SpA patients and non-SpA controls. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included articles. From 482 records identified, 31 studies were included in the analysis. A number of metabolites were differentially distributed between SpA and non-SpA cases. SpA patients showed higher levels of glucose, succinic acid, malic acid and lactate in carbohydrate metabolism, higher glycerol levels and lower fatty acid (especially unsaturated fatty acid) levels in lipid metabolism, and lower levels of tryptophan and glutamine in amino acid metabolism than healthy controls. Both conventional and biological therapy of SpA can insufficiently reverse the aberrant metabolism state toward that of the controls. However, the differences in the results of metabolic profiling between patients with SpA and other inflammatory diseases as well as among patients with several subtypes of SpA are inconsistent across studies. Studies on metabolomics have provided insights into etiological factors and biomarkers for SpA. Supplementation with the metabolites that exhibit decreased levels, such as short-chain fatty acids (SCFAs), has good treatment prospects for modulating immunity. Further studies are needed to elucidate the role of disordered metabolic molecules in the pathogenesis of SpA.

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Circulatory histidine levels as predictive indicators of disease activity in takayasu arteritis

Kumar

Mehta

Kumar

et al. 2021

Analytical Science Advances

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Background and objective: Quantitative assessment of disease activity is important for effective management of patients with autoimmune inflammatory diseases (AIDs) including Takayasu arteritis (TA). Histidine supplementation alleviates inflammation and has strong anti-oxidative effects as well. The present study aims to evaluate the diagnostic potential of circulatory histidine for predicting disease activity in TA. Methods:The serum metabolic profiles on 98 TA-patients and 77 normal controls (NC) samples were measured at high-resolution 800 MHz NMR spectrometer employing standard 1D-1 H-CPMG NMR experiments. The NMR spectral data were processed and concentrations of histidine and other circulatory metabolites were estimated with respect to formate (as an internal reference) and compared using ANOVA based on Tukey's multiple comparison test and statistical significance was considered at Pvalue < 0.05. The correlations of histidine with plasma CRP and ESR levels were evaluated using Spearman-r method. Data were expressed as median (interquartile-range [IQR]).Results: Histidine levels were significantly decreased in active TA patients (23.90; IQR:16.10) compared to both inactive TA patients (35.50, IQR:24.30) and NC (42.80, IQR:22.10), whereas there was no significant difference between inactive TA and NC.For TA patients, the histidine levels correlated negatively with clinical markers of inflammation, that is, ESR (r = -0.19, P < .078) and with the CRP (r = -0.26, P < .013).Further, the receiver-operating-characteristic (ROC) curve analysis was performed to test the diagnostic potential of histidine for differentiating active from inactive disease. The area under the ROC curve (AUROC) value equal to 0.65 [95% CI = 0.54-0.76] revealed its moderate discriminatory ability. Compared to other circulatory metabolites, the discriminatory performance of histidine was also found to be in the moderate range (highest AUROC-value of 0.76 was found for glutamine-to-glucose ratio (QGR). Conclusion:The study demonstrated the altered circulatory histidine levels in TA patients that may serve as a surrogate marker for improving the diagnostic screening of active and inactive TA patients.

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Metabolomics analysis revealed significantly higher synovial Phe/Tyr ratio in reactive arthritis and undifferentiated spondyloarthropathy

Cited by 14 publications

References 7 publications

Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach

Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach

Metabolomic analysis in spondyloarthritis: A systematic review

Circulatory histidine levels as predictive indicators of disease activity in takayasu arteritis

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